UF Health Cancer Center researchers have found that a genetic alteration may predict the outlook for patients with Ewing sarcoma, a rare and aggressive pediatric cancer. The findings, published in Molecular Oncology, could ultimately help clinicians personalize clinical-decision-making by predicting how a patient’s tumor might respond to cancer therapies.
Ewing sarcoma forms in bone or the soft tissue surrounding bone and typically affects children and young adults. Outcomes tend to be poor when the disease has spread or comes back after treatment.
Deletion of the gene CDKN2A (p16) is one of the few recurrent genetic alterations seen in patients with Ewing sarcoma, but its clinical significance remains unclear. In the new study, a team led by Nathan Seligson, Pharm.D., used cells and patient tumor samples to evaluate whether the gene could be a biomarker to predict outcomes.
They found the growth of Ewing sarcoma cells was more highly dependent on the activation of proteins that are inactivated by the CDKN2A gene than most other cancers. In patient tumor samples, both genomic loss of CDKN2A and high expression levels of CDKN2A were associated with worse overall survival.
“These findings suggests that CDKN2A could be used to predict the prognosis for patients with Ewing sarcoma, a rare disease where no molecular markers of prognosis are well-established,” said Seligson, a clinical assistant professor in the Department of Pharmacotherapy and Translational Research in the UF College of Pharmacy in Jacksonville and a member of the UF Health Cancer Center’s Cancer Targeting and Therapeutics research program.
More research is needed to understand how to best measure and use CDKN2A as a biomarker for patients with Ewing sarcoma, he said. Next, the team will do more laboratory and clinical research studies to better understand how CDKN2A affects Ewing sarcoma at different stages of the disease.
“With collaborations across the UF Health Cancer Center, we are developing tools to more accurately measure CDKN2A status in patient tumors and developing better laboratory models to study the biologic role of CDKN2A in Ewing sarcoma,” said Seligson, adding that the research team is grateful to patients and their families for supporting the research.
“Their support is the key to a healthier future,” he said.
Anjali Paragji, a Pharm.D. candidate at the UF College of Pharmacy, was the study’s first author. UF Health Cancer Center members who co-authored the paper were John Ligon, M.D., Leighton Elliott, M.D., Paul Castillo-Caro, M.D., Jatinder Lamba, Ph.D., and Elias Sayour, M.D. The study was funded through a startup research grant from the UF College of Pharmacy and UF Health Jacksonville Center for Research Training.
